S. Vogel et al. / Tetrahedron Letters 51 (2010) 1459–1461
1461
O
O
Acknowledgments
H
H
H
H
S
S
p-Tol
p-Tol
CNRS and UPMC are acknowledged for financial support. The
sponsorship of COST Action D40 ‘Innovative Catalysis: New Pro-
cesses and Selectivities’ is kindly acknowledged.
+
O
O
N
N
Bn
Bn
Zn
aq. NH4Cl
References and notes
6a
d.r. = 85/15
6b
1. For reviews, see: (a) Tsuji, J. In Handbook of Organopalladium Chemistry for
Organic Synthesis; Negishi, E.-I., Ed.; John Wiley & Sons: NY, 2002; pp 1669–
1844; (b) Trost, B. M.; Vranken, D. L. V. Chem. Rev. 1996, 96, 395–422; (c) L.S.
Hegedus, Transition Metals in the Synthesis of Complex Organic Molecules,
University Science Book, Mill Valley, 1994.
1. H2, Pd/C, EtOH, 90%.
2. LiAlH4, Et2O, reflux, 90%.
3. H2, Pd/C, MeOH then HCl.Et2O
then BzCl, NEt3, CH2Cl2, 18%.
2. Giambastiani, G.; Pacini, B.; Porcelloni, M.; Poli, G. J. Org. Chem. 1998, 63, 804–
807.
O
N
N
3. (a) Poli, G.; Giambastiani, G. J. Org. Chem. 2002, 67, 9456–9459; (b) Lemaire, S.;
Giambastiani, G.; Prestat, G.; Poli, G. Eur. J. Org. Chem. 2004, 2840–2847; (c) Bui
The Thuong, M.; Sottocornola, S.; Prestat, G.; Broggini, G.; Madec, D.; Poli, G.
Synlett 2007, 1521–1524; See also: (d) Craig, D.; Hyland, C. J. T.; Ward, S. E.
Synlett 2006, 2142–2144.
Bn
7
Bz
8
[α]20D = -59 (c = 0.7, CH2Cl2)
e.r. 85/15
4. Bantreil, X.; Prestat, G.; Madec, D.; Fristrup, P.; Poli, G. Synlett 2009, 1441–
1444.
Scheme 3. Determination of the absolute configuration for the major
5. For palladium-catalyzed allylic alkylation of
a-sulfonyl activated
diastereoisomer.
carbanions, see: (a) Giambastiani, G.; Poli, G. J. Org. Chem. 1998, 63,
9608–9609; (b) Cuvigny, T.; Julia, M.; Rolando, C. J. Organomet. Chem.
1985, 285, 395–413; (c) Colobert, F.; Genêt, J.-P. Tetrahedron Lett. 1985, 26,
system led to an inversion of the diastereoselectivity, affording the
sulfinyl-pyrrolidin-2-ones 6a and 6b in, respectively, 30:70 and
40:60 diastereomeric ratios (entries 3 and 4).
Coming back to the CH2Cl2/H2O system, use of enantiopure (S)-
Binap and (R)-Binap ligands afforded the sulfinyl-pyrrolidinones
6a–b in 61% and 95% yield, and 85:15 and 50/50 diastereomeric ra-
tios, respectively (entries 5 and 6). On the other hand, switching
again to toluene/H2O, the same (S)-Binap and (R)-Binap ligands
gave 6a–b in 70:30 and 20:80 diastereomeric ratios (entries 7
and 8).13
2779–2782; For palladium-catalyzed allylic alkylation of
a-sulfinyl
activated carbanions, see: (d) Hiroi, K.; Hidaka, A.; Sezaki, R.; Imamura,
Y. Chem. Pharm. Bull. 1997, 45, 769–777; (e) Hiroi, K.; Koyama, T.; Anzai,
K. Chem. Lett. 1990, 235–238.
6. For a stoichiometric example, see: (a) Trost, B. M.; Weber, L.; Strege, P.;
Fullerton, T. J.; Dietsche, T. J. J. Am. Chem. Soc. 1978, 100, 3426–3435; For a
catalytic example, see: (b) Hiroi, K.; Suzuki, Y.; Kato, F.; Kyo, Y. Tetrahedron:
Asymmetry 2001, 12, 37–40.
7. For relevant references concerning the use of sulfoxide-ligands in palladium-
catalysis, see: (a) Fernandez, I.; Khiar, N. Chem. Rev. 2003, 103, 3651–3706; (b)
Hanquet, G.; Colobert, F.; Lanners, S.; Solladié, G. Archivoc 2003, 7, 328–401; (c)
Mellah, M.; Voituriez, A.; Schulz, E. Chem. Rev. 2007, 107, 5133–5209; (d)
Madec, D.; Mingoia, F.; Macovei, C.; Maitro, G.; Giambastiani, G.; Poli, G. Eur. J.
Org. Chem. 2005, 552–557.
8. Madec, D.; Prestat, G.; Martini, E.; Fristrup, P.; Poli, G.; Norrby, P.-O. Org. Lett.
2005, 7, 995–998.
9. Maitro, G.; Prestat, G.; Madec, D.; Poli, G. Synlett 2006, 1055–1058.
10. Trost, B. M.; Salzmann, T. N.; Hiroi, K. J. Am. Chem. Soc. 1976, 98,
4887–4902.
Assignment of the relative configuration the diastereomeric
sulfoxides 6a and 6b was established through conversion of the
85:15 mixture as from entry 5 of Table 2 into (S)-N-benzoyl-3-eth-
ylpyrrolidine and comparison of its optical rotation with that re-
ported for the enantiopure R-configurated sample.14 Accordingly,
zinc-mediated desulfinylation of 6a–b15 yielded the corresponding
vinyl-pyrrolidone 7 without any trace of the 1,3-diene arising from
sulfenic acid elimination. Pd/C-catalyzed hydrogenation of the lat-
ter afforded the corresponding saturated lactam, which was sub-
mitted to LiAlH4 reduction to give N-benzyl-3-ethylpyrrolidine.
Finally, hydrogenolysis followed by immediate N-benzoylation
11. Xu, L.; Cheng, J.; Trudell, M. L. J. Org. Chem. 2003, 68, 5388–5391.
12. The use of OxoneÒ and wet alumina in refluxing chloroform (Greenhalgh, R. P.
Synlett 1992, 235–236) afforded sulfone 4 in poor yield (28% y) together with
the corresponding 1,3-diene (72% y).
13. General procedure for palladium-catalyzed intramolecular allylic alkylation
under biphasic conditions: To
a solution of tetrabutylammonium bromide
(46.3 mg, 0.14 mmol, 10 mol %) in dichloromethane (2.5 mL) under neutral
atmosphere were added allylpalladium chloride dimer (26.3 mg,
0.07 mmol, 5 mol %) and dppe (68.7 mg, 0.17 mmol, 12.5 mol %). The
gave N-benzoyl-3-ethylpyrrolidine 8, which showed an ½a D20
ꢀ59
ꢁ
(c 0.7, CH2Cl2). Since the sample of enantiopure R 8 reported by Ped-
solution was stirred at room temperature for 5 min. Then,
a solution of
rosa and co-workers14 had an ½a D20
ꢁ
+104 (c 0.7, CH2Cl2), the relative
acyclic substrate (574 mg, 1.43 mmol in 12.5 mL of dichloromethane),
5
13 mL of water and 50% KOH aqueous solution (0.213 mL, 2.87 mmol,
2 equiv) were successively added. The resulting biphasic system was
configurations of 6a and 6b were attributed as indicated in Scheme
3. Therefore, we can conclude that, when the reaction is conducted
in CH2Cl2, the (R)-configurated sulfoxide stereocenter favors an (R)-
configurated C-4 stereocenter on the pyrrolinone ring, whereas the
corresponding (S)-configurated C-4 stereocenter is privileged when
the reaction is carried out in toluene. Such solvent effect is exalted
upon using the appropriate matching BINAP enantiomeric form.
Specifically, (S)-Binap/CH2Cl2 (entry 5) and (R)-Binap/toluene (en-
try 8) represent the matching ligand/solvent combination.
stirred vigorously at room temperature for 2 h.
A saturated aq NH4Cl
solution (15 mL) was added and the aqueous phase was extracted with
Et2O (3 ꢂ 15 mL). The collected organic phases were washed with brine
(15 mL), dried over MgSO4 and the solvent was removed in vacuo. The
crude product was purified by flash chromatography (1:1 AcOEt/
cyclohexane). Major diastereomer 6a: 1H NMR (CDCl3, 400 MHz): d 7.53–
7.55 (m, 2H), 7.25–7.33 (m, 5H), 7.01–7.04 (m, 2H), 5.78 (m, 1H), 5.12 (d,
1H, J = 11.1 Hz), 5.09 (d, 1H, J = 4.0 Hz), 4.59 (d, 1H, J = 14.6 Hz), 4.03 (d,
1H, J = 14.6 Hz), 3.31 (m, 1H), 3.99 (d, 1H, J = 3.8 Hz), 2.83 (dd, 1H, J = 10.1,
3.5 Hz), 2.60 (dd, 1H, J = 8.3, 10.1 Hz), 2.42 (s, 3H). 13C NMR (CDCl3,
100 MHz): d 166.4, 142.2, 138.0, 136.0, 135.1, 129.7, 128.7, 128.2, 127.8,
In summary, we have reported a new and operationally very
simple protocol for the intramolecular palladium-catalyzed allylic
alkylation of a-sulfinyl carbanions, a transformation not satisfacto-
125.1, 116.5, 70.3, 50.4, 46.7, 33.1, 21.6. IR (neat):
1493, 1493, 1443, 1257, 1048, 1016 cmꢀ1 MS (CI–NH3) m/z: 340 (MH+).
HRMS m/z calcd for C20H21NNaO2S (MNa+) 362.11907, found 362.11852.
+94.0 (c 1.06 in CHCl3). Minor diastereomer 6b: 1H NMR (CDCl3,
400 MHz): 7.24–7.51 (m, 9H), 5.23–5.31 (m, 1H), 4.65 (d, 1H,
m (tilde) = 2922, 1686,
.
½ ꢁ
a 2D0
rily achievable under classical conditions. The new reaction
conditions allow the preparation of enantiopure sulfinyl-pyrroli-
din-2-ones in good yields. The concomitant use of an enantiopure
sulfinyl-derived substrate and an enantiopure atropo-isomeric
ligand under biphasic (CH2Cl2/H2O or toluene/H2O) conditions al-
lowed to obtain opposite diastereoselectivites with clearly solvent
effects. Applications of this cyclization process for the synthesis of
chiral compounds of biological interest are currently under
investigation.
d
J = 10.4 Hz), 4.54 (s, 2H), 4.48 (d, 1H, J = 16.9 Hz), 3.49 (m, 1H), 3.43 (m,
2H), 3.01 (dd, 1H, J = 4.6, 9.2 Hz), 2.41 (s, 3H). 13C NMR (CDCl3, 100 MHz):
d 167.9, 141.6, 137.9, 137.0, 135.4, 129.9, 128.9, 128.2, 128.1, 124.3, 116.3,
72.0, 50.9, 47.3, 31.1, 21.5. ½a D20
ꢁ
+297.0 (c 0.96 in CHCl3).
14. Andrés, C.; Duque-Soladana, J. P.; Pedrosa, R. J. Org. Chem. 1999, 64,
4273–4281.
15. Holton, R. A.; Crouse, D. J.; Williams, A. D.; Kennedy, R. M. J. Org. Chem. 1987,
52, 2317–2318.